Pharmacokinetic and biodistribution profile of recombinant human interleukin-10 following intravenous administration in rats with extensive liver fibrosis

Rachmawati, H., Beljaars, L., Reker-Smit, C., van Loenen - Weemaes, A., Hagens, W. I., Meijer, D. K. F. & Poelstra, K., Nov-2004, In : Pharmaceutical Research. 21, 11, p. 2072 - 2078 7 p.

Research output: Contribution to journalArticleAcademicpeer-review

Purpose. Because interleukin-10 (IL-10) seems a promising new antifibrotic drug, we investigated the pharmacokinetic and biodistribution profile of this potent therapeutic cytokine in rats with extensive liver fibrosis (BDL-3). IL-10 receptor expression was also determined in relation to these aspects.

Methods. To study the pharmacokinetic and biodistribution of IL-10, rhIL-10 was labeled with 125-iodine. Plasma samples of (125)IrhIL-10 were obtained over a 30-min time period after administration of radiolabeled-cytokine to BDL-3 and normal rats. The tissue distribution was assessed 10 and 30 min after i.v. administration of (125)IrhIL-10. IL-10 receptor expression was determined by immunohistochemical staining and RT-PCR technique.

Results. The (125)IrhIL-10 plasma curves followed two-compartment kinetics with a lower AUC in BDL-3 rats as compared to control. Plasma clearance and distribution volume at steady state were larger in BDL-3 rats. Tissue distribution analysis in normal rats showed that (125)IrhIL-10 highly accumulated in kidneys. In BDL-3 rats, the liver content of (125)IrhIL-10 increased by a factor of 2, whereas kidney accumulation did not significantly change. Immunohistochemical staining and RT-PCR analysis showed that IL-10 receptor was clearly upregulated in BDL-3 rat livers.

Conclusions. In normal rats, (125)IrhIL-10 rapidly disappears from the circulation, and the kidney is predominantly responsible for this. In BDL-3 rats, the liver largely contributes to this rapid plasma disappearance, probably due to an increase in IL-10 receptor expression. The extensive renal clearance of IL-10 in vivo may limit a clinical application of this cytokine for the treatment of chronic liver diseases. To optimize the therapeutic effects of IL-10 in hepatic diseases, alternative approaches that either decrease renal disposition or that further enhance hepatic delivery should be considered.

Original languageEnglish
Pages (from-to)2072 - 2078
Number of pages7
JournalPharmaceutical Research
Issue number11
Publication statusPublished - Nov-2004


  • cytokine, extensive liver fibrosis, IL-10 receptor, immunohistochemical staining, rhIL-10, HEPATIC STELLATE CELLS, IL-10 RECEPTOR, KUPFFER CELLS, IN-VITRO, EXPRESSION, MICE

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